Skip to main content

Advertisement

Log in

Intra-prefrontal cyclosporine potentiates ketamine-induced fear extinction in rats

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Several brain regions, including the medial prefrontal cortex (mPFC), are important in the process of fear extinction learning. Ketamine is a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, which is shown to play a role in extinction modulation. Ketamine and calcineurin (CN), an intracellular protein phosphatase, have several common targets in the cells. Therefore, in the present study, our aim is to investigate the possible role of calcineurin in the mPFC on the enhancing effects of ketamine in fear extinction. First, different doses of a CN inhibitor, cyclosporine-A (CsA), were micro-injected into the infralimbic (IL) region of the mPFC prior to extinction training in a classical conditioning model in rats. Next, sub-effective doses of CsA (Intra-mPFC) and ketamine (i.p.) were co-administered in another cohort of rats to find their possible interactions. Enzymatic activity of calcineurin was measured in the IL-mPFC following drug administration. We used the elevated plus-maze (EPM) and open field (OF) test for further behavioral assessments. The results showed that CsA can enhance the extinction of conditioned fear and inhibit the enzyme CN at a dose of 20 nM. The combination of sub-effective doses of CsA (5 nM) and ketamine (10 mg/kg) could again enhance the extinction of fear and reduce CN activity in the region. Our results propose that inhibition of CN in the IL-mPFC is involved in the extinction of fear and ketamine enhancement of extinction is probably mediated by reducing CN activity in this part of the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Availability of data and materials

Data available upon reasonable request.

References

Download references

Acknowledgements

The content of this paper is extracted from the Pharm. D thesis submitted by Negin Tamasoki which was financially supported (Grant no. 980137) by the Deputy for Research and Technology of Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

Author information

Authors and Affiliations

Authors

Contributions

AMF and NT: conceptualization, designed of the experiments, data collection, writing the first draft. RR: conceptualization, data analysis, editing. All the authors critically reviewed the contents and approved the final version of the manuscript.

Corresponding author

Correspondence to Ahmad Mohammadi-Farani.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

Animal experiment protocols were approved by the local ethical committee (ethical code, IR.KUMS.1397.849).

Additional information

Communicated by Sreedharan Sajikumar.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 65 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohammadi-Farani, A., Tamasoki, N. & Rahimian, R. Intra-prefrontal cyclosporine potentiates ketamine-induced fear extinction in rats. Exp Brain Res 239, 1401–1415 (2021). https://doi.org/10.1007/s00221-021-06050-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-021-06050-7

Keywords

Navigation